title: Urea and NaCl regulate UT-A1 urea transporter in opposing directions via TonEBP pathway during osmotic diuresis.
abstract: In our previous studies of varying osmotic diuresis, UT-A1 urea transporter increased when urine and inner medullary (IM) interstitial urea concentration decreased. The purposes of this study were to examine 1) whether IM interstitial tonicity changes with different urine urea concentrations during osmotic dieresis and 2) whether the same result occurs even if the total urinary solute is decreased. Rats were fed a 4% high-salt diet (HSD) or a 5% high-urea diet (HUD) for 2 wk and compared with the control rats fed a regular diet containing 1% NaCl. The urine urea concentration decreased in HSD but increased in HUD. In the IM, UT-A1 and UT-A3 urea transporters, CLC-K1 chloride channel, and tonicity-enhanced binding protein (TonEBP) transcription factor were all increased in HSD and decreased in HUD. Next, rats were fed an 8% low-protein diet (LPD) or a 0.4% low-salt diet (LSD) to decrease the total urinary solute. Urine urea concentration significantly decreased in LPD but significantly increased in LSD. Rats fed the LPD had increased UT-A1 and UT-A3 in the IM base but decreased in the IM tip, resulting in impaired urine concentrating ability. The LSD rats had decreased UT-A1 and UT-A3 in both portions of the IM. CLC-K1 and TonEBP were unchanged by LPD or LSD. We conclude that changes in CLC-K1, UT-A1, UT-A3, and TonEBP play important roles in the renal response to osmotic diuresis in an attempt to minimize changes in plasma osmolality and maintain water homeostasis.
authors.affiliation: Dept. of Pediatrics, The Catholic Univ. of Korea, Uijeongbu St. Mary's Hospital, 65-1 Kumoh-Dong, Uijeongbu 480-717, Republic of Korea. yumikim@catholic.ac.kr
authors.forename: Yu-Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Wan-Young
authors.initials: WY
authors.lastname: Kim
authors.forename: Hyun-Wook
authors.initials: HW
authors.lastname: Lee
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: H Moo
authors.initials: HM
authors.lastname: Kwon
authors.forename: Janet D
authors.initials: JD
authors.lastname: Klein
authors.forename: Jeff M
authors.initials: JM
authors.lastname: Sands
authors.forename: Dongun
authors.initials: D
authors.lastname: Kim
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000378:metabolism; D004044:Dietary Proteins / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009995:Osmosis / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012965:Sodium Chloride / Q000378:metabolism / Q000494:pharmacology*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014508:Urea / Q000494:pharmacology* / Q000652:urine; D000096982:Urea Transporters
chemical_list: D018118:Chloride Channels; D004044:Dietary Proteins; D026901:Membrane Transport Proteins; D012965:Sodium Chloride; D017673:Sodium Chloride, Dietary; D014157:Transcription Factors; D014508:Urea; D000096982:Urea Transporters; C082118:Clcnka protein, rat; C492199:Nfat5 protein, rat